Niu Yunfeng, Guo Yanli, Li Yan, Shen Supeng, Liang Jia, Guo Wei, Dong Zhiming
Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Exp Cell Res. 2022 Jul 15;416(2):113130. doi: 10.1016/j.yexcr.2022.113130. Epub 2022 Mar 30.
Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor worldwide. Long noncoding RNAs (lncRNAs) exhibit a regulatory role in the progression of ESCC. Our research was performed to investigate the potential molecular mechanism of lncRNA GATA2-AS1 in ESCC.
The expression of GATA2-AS1 was identified by qRT-PCR. Cell function assays explored the potential effect of GATA2-AS1 on ESCC progression. The subcellular hierarchical localization method was executed to identify the subcellular localization of GATA2-AS1 in ESCC cells. A prediction website was utilized to discover the relationships among GATA2-AS1, miR-940 and PTPN12. Dual luciferase reporter gene, pull-down assays and RIP assays were executed to verify the binding activity among GATA2-AS1, miR-940 and PTPN12. Xenograft tumor experiments were performed to evaluate ESCC cell growth in vivo.
The expression of GATA2-AS1 and PTPN12 was reduced, while miR-940 expression was enhanced in ESCC tissues and cell lines. In vivo experiments showed that GATA2-AS1 inhibited the progression of ESCC cells toward malignancy. Bioinformatics analysis, dual luciferase and RIP assays revealed that GATA2-AS1 upregulated PTPN12 expression by competitively targeting miR-940. miR-940 reversed the inhibitory effect of GATA2-AS1 on the biological behavior of ESCC cells.
Our findings suggested that GATA2-AS1, expressed at low levels in ESCC, plays a crucial role in the progression of ESCC by targeting the miR-940/PTPN12 axis and could be a potential drug target to treat ESCC patients.
食管鳞状细胞癌(ESCC)是全球常见的恶性肿瘤。长链非编码RNA(lncRNAs)在ESCC进展中发挥调节作用。我们开展本研究以探究lncRNA GATA2-AS1在ESCC中的潜在分子机制。
通过qRT-PCR鉴定GATA2-AS1的表达。细胞功能实验探究GATA2-AS1对ESCC进展的潜在影响。采用亚细胞分级定位方法鉴定GATA2-AS1在ESCC细胞中的亚细胞定位。利用预测网站发现GATA2-AS1、miR-940和PTPN12之间的关系。进行双荧光素酶报告基因、下拉实验和RIP实验以验证GATA2-AS1、miR-940和PTPN12之间的结合活性。进行异种移植肿瘤实验以评估ESCC细胞在体内的生长情况。
在ESCC组织和细胞系中,GATA2-AS1和PTPN12的表达降低,而miR-940表达增强。体内实验表明GATA2-AS1抑制ESCC细胞向恶性进展。生物信息学分析、双荧光素酶和RIP实验显示GATA2-AS1通过竞争性靶向miR-940上调PTPN12表达。miR-940逆转了GATA2-AS1对ESCC细胞生物学行为的抑制作用。
我们的研究结果表明,在ESCC中低表达的GATA2-AS1通过靶向miR-940/PTPN12轴在ESCC进展中起关键作用,可能是治疗ESCC患者的潜在药物靶点。